Jackson–Weiss syndrome (JWS) is a

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

characterized by foot abnormalities and the premature fusion of certain bones of the skull (

craniosynostosis Craniosynostosis is a condition in which one or more of the fibrous sutures in a young infant's skull prematurely fuses by turning into bone (ossification), thereby changing the growth pattern of the skull. Because the skull cannot expand perpe ...

), which prevents further growth of the skull and affects the shape of the head and face. This genetic disorder can also sometimes cause

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...

and

crossed eyes Strabismus is a vision disorder in which the eyes do not properly align with each other when looking at an object. The eye that is focused on an object can alternate. The condition may be present occasionally or constantly. If present during a ...

. It was characterized in 1976.subscription required

Signs and symptoms

Many of the characteristic facial features (among other) of Jackson–Weiss syndrome result from the premature fusion of the skull bones. The following are some of the more common, such as: * Preaxial foot

polydactyl Polydactyly or polydactylism (), also known as hyperdactyly, is an anomaly in humans and animals resulting in supernumerary fingers and/or toes. Polydactyly is the opposite of oligodactyly (fewer fingers or toes). Signs and symptoms In humans ...

* Tarsal synostosis *

Frontal bossing Skull bossing is a descriptive term in medical physical examination indicating a protuberance of the skull, most often in the frontal bones of the forehead ("frontal bossing"). Although prominence of the skull bones may be normal, skull bossing m ...

Proptosis Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen in ...

Genetics

Mutations in the

FGFR2 Fibroblast growth factor receptor 2 (FGFR2) also known as CD332 (cluster of differentiation 332) is a protein that in humans is encoded by the ''FGFR2'' gene residing on chromosome 10. FGFR2 is a receptor for fibroblast growth factor. The protein ...

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

cause Jackson–Weiss syndrome. The FGFR2 gene produces a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

called

fibroblast growth factor receptor 2 Fibroblast growth factor receptor 2 (FGFR2) also known as CD332 (cluster of differentiation 332) is a protein that in humans is encoded by the ''FGFR2'' gene residing on chromosome 10. FGFR2 is a receptor for fibroblast growth factor. The protein ...

, which occurs in chromosome number 10. Among its multiple functions, this protein signals immature cells to become bone cells in a developing

embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

. A

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

in a specific part of the FGFR2 gene alters the protein and causes prolonged signaling, which promotes the premature fusion of bones in the skull and feet,update 2011 this condition is inherited in an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

pattern. Autosomal dominant means one copy of the altered gene in each cell is sufficient to cause the disorder.

Diagnosis

The diagnosis of Jackson–Weiss syndrome in an individual suspected of having the condition is done via the following: *

Genetic testing Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...

* Clinical presentation

Differential diagnosis

The DDx for this condition includes metopic synostosis, as well as Lambdoida synostosis.

Treatment

Treatment for Jackson–Weiss syndrome can be done through surgery for some facial features and feet. Secondary complications such as

hydrocephalus Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...

cognitive Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...

impairment, can be averted via prompt surgery.

Epidemiology

In terms of epidemiology, Jackson–Weiss syndrome is a rare genetic disorder; the overall contribution of FGFR mutation to the condition is not clear.

References

External links

{{DEFAULTSORT:Jackson-Weiss syndrome Rare syndromes Autosomal dominant disorders Syndromes affecting the eye Cell surface receptor deficiencies Syndromes with craniofacial abnormalities